Flu vaccine administration in the period before SARS-CoV-2 infection and its outcomes: An umbrella review.

Objective: The potential association between influenza vaccination and SARS-CoV-2 infection and related outcomes is still controversial. The aim of this umbrella review is to represent the impact of previous influenza vaccination and COVID-19 outcomes using evidence currently available in literature. Methods: A literature search of MEDLINE, EMBASE, Scopus, Web of Science and Cochrane Library was conducted. The paper selection was conducted using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) method by two-blinded authors. The quality of meta-analyses was assessed using the AMSTAR 2 scale (A MeaSurement Tool to Assess systematic Reviews). The outcomes investigated were SARS-CoV-2 infection after influenza vaccination, hospitalization, intensive care unit admission, mechanical ventilation and mortality. Results: The literature research identified 7 ecological studies and 6 meta-analyses. All the ecological studies show a negative relationship between influenza vaccination and COVID-19. The meta-analyses suggest a protective action of influenza vaccination against SARS-CoV-2 infection. Regarding the outcomes evaluated, only two studies reported a statistically significant reduction of 12% and of 17% in hospitalization and intensive care unit admission, respectively. Regarding mechanical ventilation, three studies showed a risk reduction of 31%, 27% and 28%. A substantial reduction of mortality risk was also observed in one study. Conclusions: These results suggest that influenza vaccination could be associated with reduced susceptibility to SARS-CoV-2 infection, mechanical ventilation and mortality. Our findings highlighted how the administration of flu vaccine in subjects at risk could lead to a reduction in mortality, particularly in the over 65y.

The Burden of Modifiable Cardiovascular Risk Factors in a Population of Central Italy: A Pilot Study.

BACKGROUND: By the mid-20th century, cardiovascular disease (CVD) had become an important cause of mortality and morbidity in developed countries. The aim was to set up a pilot study to screen citizens aged 45-59 in order to identify modifiable risk factors (RFs). METHODS: Our study was conducted from February 2019 to February 2020 on citizens of a population of central Italy, aged 45-59, contacted by letter. The variables evaluated were lipid profile, glycemia, anthropometric parameters, lifestyle and utility of screening. RESULTS: It is important to underline that from the comparison with Italian national data, our results showed that blood pressure and lipid profile had better values. On the contrary, there were some alarm bells: a high percentage (57%) of smokers (63.9 in men and 37.1 in women), a sedentary lifestyle (24.5%), and a significantly higher waist circumference than the reference cut-offs for both men and women. The organization of the screening was considered excellent by 56.3% of women and 48.4% of men, and good by 37.5% of women and 46.5% of men. CONCLUSIONS: Our study provides a picture to stakeholders of the state of the health of citizens in the area under study, in the immediate pre-pandemic period; however, it is important to underline that their state of health may be modified after the pandemic period. Furthermore, cardiovascular (CV) screening was perceived by the citizens to be important for health care.

The Effects of the Ukrainian Conflict on Oncological Care: The Latest State of the Art.

BACKGROUND: The COVID-19 pandemic has dramatically affected all aspects of the patient's pathway to cancer diagnosis and subsequent treatment. Our main objective was to evaluate the status of cancer trials in Ukraine as of September 2022. METHODS: Initially, we examined with a narrative review the state of breast, colorectal, and cervical cancer population-based screening. Subsequently, we assessed each trial status for the years 2021 and 2022. RESULTS: Estimates of participation in breast and cervical cancer screening are different from region to region. Moreover, regarding cervical cancer screening, extremely different participation estimates were reported: 73% in 2003 vs. <10% 2020. Our data show that from 2014 to 2020, despite the pandemic, cancer trials in Ukraine significantly increased from 27 to 44. In 2021 no trials were completed; in fact, we observed that out of 41 trials, 8 were active not recruiting, 33 were recruiting, and 0 were completed or terminated. In 2022 in Ukraine, for oncological pathologies, only 3 trials were registered, while in 2021, 41 trials were registered. The suspension of trials regarded above all concern hematological tissue (66.7%) and the genitourinary tract (60%). CONCLUSIONS: Our work has highlighted how the areas most affected by the conflict present criticalities in oncological care.

Impact of SARS-CoV-2 Outbreak on Emergency Department Presentation and Prognosis of Patients with Acute Myocardial Infarction: A Systematic Review and Updated Meta-Analysis.

We performed an updated meta-analysis to robustly quantify admission trends of patients with ST-segment elevation MI (STEMI) and non-ST-segment elevation MI (NSTEMI) during the first wave of the pandemic and to characterize on a large basis the risk profile and early prognosis. Studies having the same observation period for the comparison between SARS-CoV-2 outbreak in 2020 versus control period in 2019 were included. Primary endpoints were the relative variation of hospital admissions, the difference of in-hospital mortality for STEMI and NSTEMI. Secondary were: mortality according to countries, income levels and data quality; cardiogenic shock, mechanical complications, door-to-balloon time, time from symptom onset to first medical contact, left ventricular ejection fraction (LVEF) and troponin. In total, 61 observational studies with 125,346 patients were included. Compared with 2019, during the pandemic for STEMI were observed: a 24% reduction of hospitalizations with an impact on early survival (OR = 1.33 in-hospital mortality); the time from symptom onset to first medical contact was 91.31 min longer, whereas door-to-balloon time was increased (+5.44 min); after STEMI, the rate of cardiogenic shock was 33% higher; LVEF at discharge was decreased (-3.46); elevated high-sensitivity troponin levels (1.52) on admission. For NSTEMI, in the COVID-19 period, we observed a 31% reduction of hospitalizations and higher in-hospital deaths (OR = 1.34). The highest mortality rates among countries were: Italy OR = 3.71 (high income), Serbia OR = 2.15 (upper middle) and Pakistan OR = 1.69 (lower middle). Later hospital presentation was associated with larger infarctions, as well as with increased cardiogenic shock and in-hospital mortality.

Abdominal Aortic Screening Is a Priority for Health in Smoker Males: A Study on Central Italian Population.

Abdominal aortic aneurysm (AAA) is a major public health problem. In the last decade, in some European countries, abdominal aortic screening (AAS) is emerging as a potential prevention for the rupture of AAA. The goals of our study were to estimate AAA prevalence and risk factors in males and females in a central Italian population, also defining the cost-effectiveness of AAS programs. A pilot study screening was conducted between 1 January 2015 and 31 December 2019 in the municipality of Teramo (Abruzzo Region, Italy) in a group of men and women, ranging from the age of 65 to 79, who were not previously operated on for AAA. The ultrasound was performed by means of Acuson sequoia 512 Simens with a Convex probe. The anterior posterior of the infra-renal aorta was evaluated. The odds ratio values (ORs) were used to evaluate the risk of AAA, and the following determinants were taken into consideration: gender, smoke use, hypertension, and ischemic heart disease. We also estimated the direct costs coming from aneurysmectomy (surgical repair or endovascular aneurysms repair-EVAR). A total of 62 AAA (2.7%, mean age 73.8 ± 4.0) were diagnosed, of which 57 were in men (3.7%, mean age 73.6 ± 4.0) and 5 were in women (0.7%, mean age 74.3 ± 4.1). Male gender and smoke use are more important risk factors for AAA ≥ 3 cm, respectively: OR = 5.94 (2.37-14.99, p < 0.001) and OR = 5.21 (2.63-10.30, p < 0.000). A significant increase in OR was noted for AAA ≥ 3 cm and cardiac arrhythmia and ischemic heart disease, respectively: OR = 2.81 (1.53-5.15, p < 0.000) and OR = 2.76 (1.40-5.43, p = 0.006). Regarding the cost analysis, it appears that screening has contributed to the reduction in costs related to urgency. In fact, the synthetic indicator given by the ratio between the DRGs (disease related group) relating to the emergency and those of the elective activity went from 1.69 in the year prior to the activation of the screening to a median of 0.39 for the five-year period of activation of the screening. It is important to underline that the results of our work confirm that the screening activated in our territory has led to a reduction in the expenditure for AAA emergency interventions, having increased the planned interventions. This must be a warning for local stakeholders, especially in the post-pandemic period, in order to strengthen prevention.

Serum Calprotectin a Potential Biomarker in Juvenile Idiopathic Arthritis: A Meta-Analysis.

Juvenile idiopathic arthritis (JIA) is the most common inflammatory chronic disease affecting children and adolescents. Today, there are no specific biomarkers of inflammation. Therefore, it is important to identify new markers as predictors of disease activity. Recently, some researchers have directed their interest toward a protein, calprotectin (CLP), as a potential biomarker. The primary objective of our systematic review and meta-analysis was to analyze the possible role of CLP in JIA. METHOD: A literature search was conducted using PubMed, EMBASE, Scopus, Science Direct on 10 August 2021. The selection of studies was made using the PRISMA 2020 guidelines. Cohen's d with 95% CI and p-value were used as a measure of effect size. The random effects model was used to account for different sources of variation among studies. Heterogeneity was assessed using Q statistics and I2. The publication bias was analyzed and represented by a funnel plot, and funnel plot symmetry was assessed with Egger's test. RESULTS: Our results at follow-up showed a statistically significant difference between patients with active disease compared to patients with inactive disease: 0.39 (0.16; 0.62), p = 0.001; without statistical heterogeneity. Another important aspect that emerged were the differences between the systemic disease form and any form of inactive disease showing a different concentration of calprotectin: 0.74 (0.40; 1.08), p < 0.001; without statistical heterogeneity. On the other hand, meta-regression analyses performed on gender, age, duration of disease, percentage of patients with ANA+ or RF+, medium value of ESR or CRP were not statistically significant. A statistically significant difference in serum calprotectin concentration between patients with JIA and healthy controls were observed. In fact, it presented lower values in the control group. CONCLUSIONS: The use of serum CLP could represent, in the future, a useful tool in JIA in order to stratify disease activity more accurately and may aid a more tailored approach to drug of choice in children with JIA. Further studies are needed to evaluate CLP as a predictor of flare in combination with other potential biomarkers of subclinical disease activity.

Assessment of Pain and Associated Comorbidities: A Survey of Real Life Experiences Among Nurses in Italy.

PURPOSE: Pain is a symptom that should be evaluated along with its comorbidities in order to plan an effective holistic treatment strategy involving specific pharmacological interventions, side effect management, psychological support, control of therapeutic effects over time, and dialogue with the patient and their relatives. In this holistic process of caring for patients with pain, nurses play a central role as they deal with suffering patients directly and continuously. The purpose of this study was to evaluate the types of pain identified by nurses in their daily clinical practice and the associated comorbidities (anamnestic history taking) by geographical region and to evaluate the pharmacological strategies used. METHODS: A cross-sectional survey was performed among 696 registered nurses in Italy. Data were collected using an online questionnaire. RESULTS: There was a significant difference between geographical regions in terms of reports of acute and chronic pain: acute pain was more frequently reported in the South (63.5%), while chronic pain was more frequent in the Central region (32.3%; p=0.0008). Additionally, chronic oncological pain was more frequent in the Northeast (29.6%), while chronic non-oncological pain was more frequently reported in the Central region (33.9%; p=0.0001). The underlying pain disorders reported were also different between geographical regions; rheumatic pain (21.8%) and neurological pain (18.6%) were more frequent in the Central region, while musculoskeletal pain was significantly more frequent in the South (43.4%; p=0.004). Anxiety, sleep disorders and somatization were found in acute pain (60.82%, 43.56% and 53.12%), while depression and mood disorders were more frequently detected in chronic pain condition (p<0.001). CONCLUSION: Our study showed differences among Italian regions in pain assessment. Specific education on pain management nursing is essential for nurses. Promotion of optimal nursing care for people affected by pain is the main focus of pain management nursing. Nowadays, nurses should focus on personalized complex care and research in order to improve the patient's quality of life.

Potential Therapeutic Effects of Curcumin on Glycemic and Lipid Profile in Uncomplicated Type 2 Diabetes-A Meta-Analysis of Randomized Controlled Trial.

Diabetes mellitus is an important issue for public health, and it is growing in the world. In recent years, there has been a growing research interest on efficacy evidence of the curcumin use in the regulation of glycemia and lipidaemia. The molecular structure of curcumins allows to intercept reactive oxygen species (ROI) that are particularly harmful in chronic inflammation and tumorigenesis models. The aim of our study performed a systematic review and meta-analysis to evaluate the effect of curcumin on glycemic and lipid profile in subjects with uncomplicated type 2 diabetes. The papers included in the meta-analysis were sought in the MEDLINE, EMBASE, Scopus, Clinicaltrials.gov, Web of Science, and Cochrane Library databases as of October 2020. The sizes were pooled across studies in order to obtain an overall effect size. A random effects model was used to account for different sources of variation among studies. Cohen's d, with 95% confidence interval (CI) was used as a measure of the effect size. Heterogeneity was assessed while using Q statistics. The ANOVA-Q test was used to value the differences among groups. Publication bias was analyzed and represented by a funnel plot. Curcumin treatment does not show a statistically significant reduction between treated and untreated patients. On the other hand, glycosylated hemoglobin, homeostasis model assessment (HOMA), and low-density lipoprotein (LDL) showed a statistically significant reduction in subjects that were treated with curcumin, respectively (p = 0.008, p < 0.001, p = 0.021). When considering HBA1c, the meta-regressions only showed statistical significance for gender (p = 0.034). Our meta-analysis seems to confirm the benefits on glucose metabolism, with results that appear to be more solid than those of lipid metabolism. However, further studies are needed in order to test the efficacy and safety of curcumin in uncomplicated type 2 diabetes.

Lifestyle Risk Factors for Type 2 Diabetes Mellitus and National Diabetes Care Systems in European Countries.

BACKGROUND: Diabetes is increasing by 3.09% per year in males and 1.92% in females. Lifestyle risk factors are related to diabetes. The aim of this work is to highlight within EU-28 countries the distribution percentages of some lifestyle risk factors and some components of diabetes health care. METHODS: A literature search was conducted to highlight the presence of diabetes registries, which are fundamental tools for disease surveillance and health planning; the presence of a national diabetes plan (NDP); the care setting; and methods used for reimbursement of drugs, devices, and coverage of any comorbidities associated with diabetes. A multiple correspondence analysis (MCA) was carried out to evaluate the possible associations between the variables considered. RESULTS: The highest percentages of diabetes (>10%) are registered in Bulgaria, Malta, and Hungary. Concerning the prevalence of overweight, no European country shows overall percentages of less than 50%. Regarding obesity, 57% of countries show prevalence rates of 25%. The record for physical inactivity belongs to Malta, with 45% of individuals being inactive. The percentage of physical inactivity for females is higher than for males across Europe. In total, 57% of the countries have an insurance-based health system, while 12 countries have public national health systems. Further, 57% of countries have an NDP, while 42% of the EU countries have established a prevalence register for diabetes. Conclusions. Prevalence rates for type 2 DM in the range of 8-9% are noted in 50% of EU-28 countries. In total, 21 out of EU countries show a high prevalence rate for overweight, while 7% of EU-28 countries have an obesity prevalence rate of 25%. Diabetes treatment is entrusted to general practitioners in most countries. The results of this work highlight the differences between countries, but also between genders.

The Impact of Human Milk on Necrotizing Enterocolitis: A Systematic Review and Meta-Analysis.

BACKGROUND: Premature infants receiving breastfeed have a lower incidence of NEC than those fed preterm formula. This study aimed: (1) to update a systematic review and meta-analyses to evaluate the relationship between feeding and necrotizing enterocolitis (NEC) in low weight premature infants; (2) to conduct meta-regression analyses by subgroups; (3) to describe geographical distribution of milk banks in the world. METHODS: Papers included in the meta-analysis were updated as of June 2019. Relative risks were used as a measure of effect size. Random effect models were used to account for different sources of variation among studies. For milk banks, the data reviewed by the literature were integrated with the information collected from countries' institutional sites and milk bank networks. RESULTS: Thirty-two papers were included in meta-analysis: six randomized controlled trials (RCTs) and 26 observational studies (OS). The census has found 572 milk banks around in the world. Brazil has the most active milk banks. RCTs meta-analysis indicates a risk reduction of NEC using human milk respect to formula: Relative risk (RR) = 0.62 (0.42-0.93). Seven OS compared quantities lower than human milk or higher than the 50th quantile showing a risk reduction of NEC:RR = 0.51 (0.31-0.85); 3 OS that evaluated human milk versus mixed feeding showing that human milk has a protective role on the development of NEC:RR = 0.74 (0.63-0.91). Results of subgroups analysis show that the risk reduction is statistically significant only for studies in which premature infants are given both their own and donated breastmilk. CONCLUSIONS: The possibility of preserving human milk and promoting donations guarantees an improvement in the health of newborns.

Overview of Meta-Analyses: The Impact of Dietary Lifestyle on Stroke Risk.

A stroke is one of the most prevalent cardiovascular diseases worldwide, both in high-income countries and in medium and low-medium income countries. The World Health Organization's (WHO) report on non-communicable diseases (NCDs) indicates that the highest behavioral risk in NCDs is attributable to incorrect nutrition. The objective of our work is to present an overview of meta-analyses that have investigated the impact of different foods and/or drinks in relationship with the risk of stroke events (ischemic/hemorrhagic). The papers to be included in the overview were found in MEDLINE, EMBASE, Scopus, Clinicaltrials.gov, Web of Science, and Cochrane Library and were selected according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) flow chart. Quality assessment were made according to the AMSTAR 2 scale. This overview shows that all primary studies came from countries with high income levels. This evidence shows that many countries are not represented. Therefore, different lifestyles, ethnic groups, potentially harmful or virtuous eating habits are not reported. It is important to underline how the choose of foods may help reduce the risk of cardiovascular diseases and stroke in particular.

An Analysis of Italian Nurses' Approach to Patients' Pain: A Nationwide Online Survey.

Healthcare providers play a fundamental role in evaluating pain. Several issues about how nurses are educated remain unsolved. The aim of our study was to address how Italian nurses manage patients suffering from pain in daily practice. A cross-sectional survey was administered among Italian registered nurses. Data were collected using a 34-item questionnaire that had been previously validated during a pilot study. The lowest level of participation/education/information events was observed in the South (p=0.0001). A significant difference among the four areas was found in the department affiliation of responders (p=0.0001). Pain assessment at patients' admission was most frequent in the Northeast (32.9%), whereas the lowest frequency was found in the South (15.1%) (p=0.0001). The prevalence of nurses' knowledge of pain scales and their distribution in usual applications was similar in the Northwest and -east, and Central Italy, but lower in the South (p=0.0001). This study underlines the need for change in the clinical approach to pain treatment in healthcare. Pain assessment is a fundamental step for preparing individualized therapeutic plans, and nurses play a crucial role in improving the quality of life of suffering patients.

HtrA1 as a promising tissue marker in cancer: a meta-analysis.

BACKGROUND: HtrA1 is expressed in a variety of normal human tissues and seems to be involved in numerous physiological processes as well as tumorigenesis. This study reports the results of a meta-analysis that was performed: to compare HtrA1 expression as mRNA and protein, in cancer tissue versus non-cancer tissue and to assess overall survival in relation to low or medium-high HtrA1 tissue expression. METHODS: The PRISMA method was used for study selection. OR and HR with 95% confidence interval was used as a measure of effect size as appropriate. A random-effects model was applied to account for different sources of variation among studies. Heterogeneity across studies was assessed using Q statistic. Sensitivity analysis was conducted to check the stability of study findings. Egger's regression method was applied to test funnel plot asymmetry. RESULTS: Sensitivity analysis indicated the stability of meta-analytic findings in each meta-analysis. The study found a significantly different HtrA1 expression in cancer and non-cancer tissue. The meta-analysis of the prognostic studies showed a different survival according to HtrA1 expression. CONCLUSIONS: The present data may provide a contribution to future work directed at exploring the role of HtrA1 in tumor development and progression and at establishing whether it may be used as a promising tissue marker for some tumors.

Low-FODMAP Diet Improves Irritable Bowel Syndrome Symptoms: A Meta-Analysis.

Irritable bowel syndrome (IBS) affects 7-15% of the general population. A recently devised dietary approach consists of restricting foods with highly fermentable oligo-, di-, and monosaccharides, and polyols (FODMAPs), which can trigger and/or exacerbate IBS symptoms. The aim of this study is to use meta-analysis to provide an update on the randomised control trials (RCTs) and cohort studies, and examine them separately in relation to diet type. Papers were selected using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart. Cohen's d and odds ratios were used as a measure of effect size for RCTs. A random effects model was used to account for different sources of variation among studies. Heterogeneity was assessed using Q statistics, I², Tau, and Tau². Publication bias was analysed and represented by a funnel plot, and funnel plot symmetry was assessed with Egger's test. The results showed that in the RCTs, the patients receiving a low-FODMAP diet experienced a statistically significant pain and bloating reduction compared with those receiving a traditional diet; as regards to stool consistency, there was no significant difference between treatments. A significant reduction in abdominal pain and bloating were described by patients receiving a low-FODMAP diet compared with those receiving a high-FODMAP diet. In cohort studies, pain and bloating were significantly reduced after treatment compared with the baseline diet. We conclude that there is evidence that a low-FODMAP diet could have a favourable impact on IBS symptoms, especially abdominal pain and bloating. However, it remains to be demonstrated whether a low-FODMAP diet is superior to conventional IBS diets, especially in the long term.

Synovial Fluid and Serum Concentrations of Inflammatory Markers in Rheumatoid Arthritis, Psoriatic Arthritis and Osteoarthitis: A Systematic Review.

BACKGROUND: The aim of this review is to investigate systematically the presence of the most extensively studied Synovial Fluid (SF) and/or serum markers in patients with Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA) and Osteoarthritis (OA), and their associations and correlations with laboratory and clinical data, with a view to providing insights for future research. OBJECTIVE: Papers were selected using the PRISMA flow-chart. Search of the electronic databases according to the above criteria found a total of 55 papers. Examination led to the exclusion of 39 papers. Finally, 16 studies met the inclusion criteria and are reviewed. As regards to interleukins we found: Higher TNF-α levels in patients with early RA and PsA than in those with osteoarthritis (p<0.05); higher IL-6 levels in patients with inflammatory arthritis (RA and PsA) than in those with OA (p=0.032) and higher IL-17 levels in SF from PsA patients than RA patients (p=0.04) and a significant difference in serum levels between PsA patients and healthy controls (p=0.013) and higher IL-22 SF levels in PsA than OA patients (p<0.001) and in RA compared with OA patients (p<0.01). As regards chemokine, CCL-22 was higher in SF from RA and PsA patients than in OA patients (p<0.01). METHOD: Considering the sample size of the studies reviewed here, their findings need confirmation in larger samples, while the potential prognostic value of SF and/or serum biomarkers requires prospective investigation. CONCLUSION: The limitations of the biological SF assays and the problems encountered in the attempted use of cytokine assays for diagnostic purposes must be addressed.

Breast Cancer Screening Programmes across the WHO European Region: Differences among Countries Based on National Income Level.

Breast cancer (BC) is the most frequent tumour affecting women all over the world. In low- and middle-income countries, where its incidence is expected to rise further, BC seems set to become a public health emergency. The aim of the present study is to provide a systematic review of current BC screening programmes in WHO European Region to identify possible patterns. Multiple correspondence analysis was performed to evaluate the association among: measures of occurrence; GNI level; type of BC screening programme; organization of public information and awareness campaigns regarding primary prevention of modifiable risk factors; type of BC screening services; year of screening institution; screening coverage and data quality. A key difference between High Income (HI) and Low and Middle Income (LMI) States, emerging from the present data, is that in the former screening programmes are well organized, with approved screening centres, the presence of mobile units to increase coverage, the offer of screening tests free of charge; the fairly high quality of occurrence data based on high-quality sources, and the adoption of accurate methods to estimate incidence and mortality. In conclusion, the governments of LMI countries should allocate sufficient resources to increase screening participation and they should improve the accuracy of incidence and mortality rates.

Methylation analysis and HPV genotyping of self-collected cervical samples from women not responding to screening invitation and review of the literature.

AIM OF THE STUDY: To assess the feasibility of partial HPV genotyping and methylation analysis of CADM1, MAL, and miR124-2 genes as triage tests in assaying self-collected cervical samples positive for high-risk HPV on primary screening, and to review the literature regarding host cellular gene methylation analysis of self-collected cervical samples. MATERIAL AND METHODS: Women residing in North-East Italy who had failed to respond to the invitation to participate in an organized population-based program were invited to provide a self-sample. Their stored baseline (self-collected) and follow-up (clinician-collected) cervical samples were included in the study. DNA was extracted from HPV-positive (Qiagen's Hybrid Capture 2, HC2) samples. Partial genotyping with separate detection of HPV types 16 and 18 was performed with a hybrid capture-based method and a quantitative PCR assay. Methylation was assayed with a quantitative methylation-specific PCR. RESULTS: High-risk HPV infection was detected in 48% of baseline and 71% of follow-up HC2-positive samples. Methylation was demonstrated respectively in 15% and 23.5% of baseline and follow-up samples and chiefly involved a single gene (miR124-2). Invalid quantitative PCR results were recorded in 5% of self-collected samples. The specificity of miR124-1, MAL, and CADM1 methylation was 84%, 94%, and 98%, respectively, and the specificity of the three markers combined was 84%. Sensitivity was not estimated due to the lack of CIN2+ samples. The systematic review showed that different methylation assays yield different accuracy values. CONCLUSION: Self-collected samples are suitable for methylation assays included in reflex triage testing. The reproducibility and accuracy of the methylation tests described in the literature should be improved.

Role of Urinary Biomarkers in the Diagnosis of Adenoma and Colorectal Cancer: A Systematic Review and Meta-Analysis.

The growing interest in enhancing and spreading colorectal cancer (CRC) screening has been stimulating the exploration of novel biomarkers with greater sensitivity and specificity than immunochemical faecal occult blood test (iFOBT). The present study provides i) a systematic review of the urinary biomarkers that have been tested to achieve early CRC diagnosis and assess the risk of colorectal adenoma and adenocarcinoma, and ii) a meta-analysis of the data regarding the urinary prostaglandin (PG) metabolite PGE-M. As regard to gene markers, we found significantly different percent methylation of the vimentin gene in CRC patients and healthy controls (HC) (p<0.0001). Respect to metabolism of nitrogenous bases, cytidine, 1-methyladenosine, and adenosine, have higher concentrations in CRC patients than in HC (respectively, p<0.01, p=0.01, and p<0.01). As regard to spermine we found that N1,N12 diacetyl spermine (DiAcSpm) and N1, N8 diacetylspermidine (DiAcSpd) were significantly higher in CRC than in HC (respectively p=0.01 and p<0.01). Respect to PGE-M, levels were higher in CRC than in those with multiple polyposis (p<0.006) and HC subjects (p<0.0004). PGE-M seems to be the most interesting and promising urinary marker for CRC and adenoma risk assessment and for CRC screening. In conclusion, evidence suggests that urinary biomarker could have a potential role as urinary biomarkers in the diagnosis of colorectal cancer. Particularly, PGE-M seems to be the most promising urinary marker for CRC early detection.

Colorectal cancer screening in countries of European Council outside of the EU-28.

AIM: To provide an update on colorectal cancer (CRC) screening programmes in non-European Union (EU)-28 Council of Europe member states as of December 2015. METHODS: The mission of the Council of Europe is to protect and promote human rights in its 47 member countries. Its 19 non-EU member states are Albania, Andorra, Armenia, Azerbaijan, Bosnia and Herzegovina, Republika Srpska, Georgia, Iceland, Liechtenstein, Republic of Moldova, Monaco, Montenegro, Norway, Russian Federation, San Marino, Serbia, Switzerland, FYR of Macedonia, Turkey, and Ukraine (EU-19). The main data source were GLOBOCAN, IARC, WHO, EUCAN, NORDCAN, ENCR, volume X of the CI5, the ministerial and Public Health Agency websites of the individual countries, PubMed, EMBASE, registries of some websites and the www.cochranelibrary.com, Scopus, www.clinicaltrials.gov, www.clinicaltrialsregister.eu, Research gate, Google and data extracted from screening programme results. RESULTS: Our results show that epidemiological data quality varies broadly between EU-28 and EU-19 countries. In terms of incidence, only 30% of EU-19 countries rank high in data quality as opposed to 86% of EU-28 states. The same applies to mortality data, since 52% of EU-19 countries as against all EU-28 countries are found in the high ranks. Assessment of the method of collection of incidence data showed that only 32% of EU-19 countries are found in the top three quality classes as against 89% of EU-28 countries. For the mortality data, 63% of EU-19 countries are found in the highest ranks as opposed to all EU-28 member states. Interestingly, comparison of neighbouring countries offering regional screening shows, for instance, that incidence and mortality rates are respectively 38.9 and 13.0 in Norway and 29.2 and 10.9 in Sweden, whereas in Finland, where a national organised programme is available, they are respectively 23.5 and 9.3. CONCLUSION: Cancer screening should be viewed as a key health care tool, also because investing in screening protects the weakest in the population, decreases the social burden of cancer, and reduces all types of health care costs, including those for radical surgery, long-term hospitalisation, and chemotherapy.

HtrA1: Its future potential as a novel biomarker for cancer.

HtrA1 appears to be involved in several physiological processes as well as in the pathogenesis of conditions such as Alzheimer's disease and osteoarthritis. It has also been hypothesized to play a role as a tumor suppressor. This manuscript reviews the current cancer-related HtrA1 research from the methodological and clinical standpoints including studies regarding its potential role as a tumor marker and/or prognostic factor. PRISMA method was used for study selection. The articles thus collected were examined and selected by two independent reviewers; any disagreement was resolved by a methodologist. A laboratory researcher reviewed the methods and laboratory techniques. Fifteen studies met the inclusion criteria and concerned the following cancer sites: the nervous system, bladder, breast, esophagus, stomach, liver, endometrium, thyroid, ovaries, pleura, lung and skin. Most articles described in vivo studies using a morphological approach and immunohistochemistry, whereas protein expression was quantified as staining intensity scored by two raters. Often the results were not comparable due to the different rating scales and study design. Current research on HtrA1 does not conclusively support its role as a tumor suppressor.